Research Day

Title

Pimavanserin for Parkinson's Disease Psychosis

Document Type

Abstract

Date

2017

Abstract

Introduction: Parkinson's disease is a progressive neurodegenerative disease involving the basal ganglia affecting dopamine-secreting nigrostriatal pathway. It is diagnosed clinically by the presence of any combination of: Bradykinesia, Resting Tremor, Rigidity, Gait instability. Psychosis occurs in 20 to 40 percent of drug-treated patients with PD, and visual hallucinations are the most common psychotic symptom. Parkinsonian Psychosis treatment (with neuroleptics/antipsychotics blocking Dopamine in the mesolimbic pathway) had been a clinical challenge because it risks exacerbation of motor symptomatology. On 4/29/16, FDA approved Pimavanserin, a 5HT-2A inverse agonist, a novel antipsychotic, that addresses psychosis independently of the Dopamine pathways after successful completion of a phase 3 placebo-controlled trial. We report a case of Parkinsonian psychosis which responded well to Pimavanserin. Case Report 72 year old Caucasian female with a history of Parkinson's; motor symptoms previously stable on Carbidopa-Levodopa (Sinemet) but developing visual hallucinations secondary to Sinemet and consequently being weaned off of it by outpatient neurologist in anticipation of being initiated on Pimavanserin. Admitted for acute agitation, mild paranoia and worsening visual hallucinations (VH) with dementia ongoing for the past year. During her inpatient stay, she was completely weaned off of Sinemet and was started on Pimavanserin 17 mg bid (well-tolerated). Target psychosis symptoms (paranoia and visual hallucinations) resolved secondary to 3 days of Pimavanserin at starting dose and motor symptoms did not deteriorate after 3 days of not being on any Sinemet and she was discharged. Discussion Parkinson's Disease psychosis is the strongest predictor of nursing home placement as well as mortality. The psychosis is hypothesized to represent an imbalance between the dopamine and serotonin systems. Treatment in the past was more difficult secondary to limited pharmacological options. interestingly, Parkinson's disease was treated primarily with dopaminergic agents to reduce motor symptoms but these agents often worsened the psychosis. Similarly, Psychosis was treated primarily with antipsychotic agents, which in turn, worsened the motor symptoms. Pimavanserin, a selective serotonin 5 HT2A inverse agonist, has potent actions on 5HT2A without any dopaminergic activity/affinity. Conclusion: Due to these actions, Pimavanserin was able to significantly reduce psychotic symptoms in patients with moderate to severe Parkinson's disease, achieve efficacy without worsening motor symptoms, achieve efficacy without significant safety concerns in our patient. Our patient tolerated this medication well, showed clinically meaningful improvement in psychotic symptoms, and reduced the caregiver burden on his family.

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